Ibudilast in the Treatment of Patients With Chronic Migraine. (IBU-003)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Aalborg University
Sponsor:
Collaborators:
The Ministry of Science, Technology and Innovation, Denmark
Migraine Research Foundation
Information provided by (Responsible Party):
Parisa Gazerani, Aalborg University
ClinicalTrials.gov Identifier:
NCT01389193
First received: June 29, 2011
Last updated: October 11, 2013
Last verified: October 2013
  Purpose

This will be a double-blind, randomised, placebo-controlled, two period cross over study of ibudilast in the treatment of chronic migraine.

For participants resident in Adelaide, South Australia (i.e. "local participants"):

The study will involve a screening visit followed by eight visits to the Pain and Anaesthesia Research Clinic (PARC), within the Royal Adelaide Hospital (RAH), for baseline testing, initiation of the study medications and ongoing data collection (one baseline and three study visits during each treatment period).

At the baseline visit, blood samples to assess biomarkers (glutamate, calcitonin gene-related peptide, glial fibrillary acidic protein and S100β) will be taken. Patients will then be randomised (in a 1:1 ratio) to commence either ibudilast or placebo treatment, which will continue for 8 weeks. Subsequently participants will undergo a 4-week washout period. At the end of the washout period a second 8-week treatment block with the alternative treatment will commence.

Patients will complete a headache diary daily for at least 4 weeks prior to the baseline visit, throughout the treatment and washout periods and for 4 weeks after treatment ceases. The diary will record headache frequency, duration, intensity, pain characteristics and medication intake for comparison with baseline data.

From screening until the final study visit (over a minimum of 6 months) a total of approximately 200 mL in blood samples will be taken from each local participant.

For participants located in country or interstate locations:

The same study will be undertaken, but instead of attending the Pain and Anaesthesia Research Clinic (PARC), within the Royal Adelaide Hospital (RAH) for screening and study visits, these will be managed remotely through:

basic input from the participant's GP during the screening period correspondence with the PI and study staff via registered post, phone or Skype scheduled visits to the nearest pathology collection centre for blood biochemistry and haematology analysis

Interstate or country participants will also be exempt from collection of blood samples for biomarker analysis, hence a total of approximately 120 mL of blood samples will be taken from each interstate or country participant.


Condition Intervention Phase
Migraine Headache
Drug: Ibudilast
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Targeting Glial Inhibition to Attenuate Chronic Migraine: AN INTERNATIONAL DOUBLE-BLIND, RANDOMISED, PLACEBO-CONTROLLED TRIAL OF IBUDILAST

Resource links provided by NLM:


Further study details as provided by Aalborg University:

Primary Outcome Measures:
  • Primary efficacy end point [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]

    As suggested by the IHS guidelines for clinical trials in chronic migraine, the primary efficacy endpoint will be number of headache days per month with moderate or severe intensity. Study outcomes will be assessed at baseline and at weeks 2, 4 and 8 of each treatment period.

    To monitor treatment with ibudilast, blood biochemistry (including assessment of renal and hepatic including GGT function) and haematology will be assessed at baseline, and at weeks 2, 4 and 8 of each treatment period. Patients will also be screened for adverse effects via questionnaire at each visit during treatment.



Secondary Outcome Measures:
  • Secondary efficacy end points [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]

    The secondary end points assessed will include:

    • Migraine frequency (number of days with migraine of any severity/month)
    • Migraine episode frequency (number of migraine episodes/month)
    • Medication frequency (number of days acute headache medication taken/month)
    • Headache related impact on quality of life as assessed using the HIT-6
    • Cutaneous allodynia as assessed using the ASC-12
    • Biomarker levels

  • Serum biomarker levels [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    To determine if serum levels of the following potential biomarkers are able to differentiate response to treatment with ibudilast: glutamate, calcitonin gene-related peptide, glial fibrillary acidic protein and S100 calcium binding protein β.


Other Outcome Measures:
  • safety and tolerability of ibudilast [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    Ibudilast 40 mg or placebo twice daily for 8 weeks is effective and safe in a chronic migraine population.


Estimated Enrollment: 42
Study Start Date: June 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ibudilast Drug: Ibudilast
Ibudilast 40 mg twice daily oral capsules for a duration of 8 weeks
Other Name: Ibudilast (Ketas® 10 mg capsules) manufactured by Kyorin Pharmaceuticals.
Placebo Comparator: Placebo Drug: Placebo
Placebo 40 mg twice daily oral capsules for a duration of 8 weeks
Other Name: Pharmaceutical Packaging Professionals, West Thebarton Rd, Thebarton, South Australia

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Men and women aged between 18 to 65 years Migraine with or without aura, as diagnosed according to the second edition International Classification of Headache Disorders (ICHD-II) Onset of migraine before 50 years of age Headache on 15 or more days per month Migraine-like headache on 8 or more days per month, as per the IHS guidelines

Exclusion Criteria:

  • Change in type or dose of migraine prophylactic medication in last 3 months
  • Medication overuse headache as diagnosed according to the ICHD-IIR
  • Post-traumatic headache as diagnosed according to the ICHD-II
  • Other dominant chronic pain condition
  • Known active inflammatory diseases such as rheumatoid arthritis
  • History of recent cerebrovascular disorder
  • Unable to provide written informed consent
  • Unable to read and write in English
  • Severe psychological/psychiatric disorders
  • Recent history of significant trauma, as determined by the Principal Investigator including major surgery within the previous 2 months or major surgery planned during the treatment period
  • Recent history of drug or alcohol abuse
  • Any clinically significant findings on screening blood sample results
  • Current malignancy
  • Known hypersensitivity to ibudilast or excipients in Ketas® formulation
  • Renal or hepatic impairment, defined as baseline GFR (as calculated by the Cockcroft-Gault equation) of <60 mL/min, LFTs (excluding bilirubin) > 3 times the upper limit of normal or bilirubin > 2 times the upper limit of normal
  • For females of childbearing potential:

    • Pregnancy
    • Lack of adequate contraception (abstinence, double barrier method, intrauterine device, surgical sterilization (self or partner), hormonal contraceptive methods (oral, injected, or implanted)
    • Breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01389193

Contacts
Contact: Paul Rolan, MBBS FRACP FFPM MD +61 8 8303 4102 paul.rolan@adelaide.edu.au

Locations
Australia
School of Medical sciences, University of Adelaide Recruiting
Adelaide, Australia
Contact: Paul Rolan, MBBS FRACP FFPM MD       paul.rolan@adelaide.edu.au   
Contact: Parisa Gazerani, Pharm D, PhD       gazerani@hst.aau.dk   
Sub-Investigator: Parisa Gazerani, Pharm D, PhD         
Principal Investigator: Paul Rolan, MBBS FRACP FFPM MD         
Sponsors and Collaborators
Parisa Gazerani
The Ministry of Science, Technology and Innovation, Denmark
Migraine Research Foundation
Investigators
Principal Investigator: Paul Rolan, MBBS FRACP FFPM MD School of Medical sciences, University of Adelaide, Adelaide, Australia
Principal Investigator: Parisa Gazerani, PharmD, PhD Aalborg University
  More Information

No publications provided

Responsible Party: Parisa Gazerani, Associtae professor, Aalborg University
ClinicalTrials.gov Identifier: NCT01389193     History of Changes
Other Study ID Numbers: IBU-003, MRF and DRC
Study First Received: June 29, 2011
Last Updated: October 11, 2013
Health Authority: Australia: Human Research Ethics Committee
The Human Research Ethics Committee of the Royal Adelaide Hospital: Australia

Keywords provided by Aalborg University:
ibudilast
migraine
glial cell

Additional relevant MeSH terms:
Migraine Disorders
Brain Diseases
Central Nervous System Diseases
Headache Disorders
Headache Disorders, Primary
Nervous System Diseases
Ibudilast
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Enzyme Inhibitors
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Phosphodiesterase Inhibitors
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Respiratory System Agents
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on October 29, 2014